**1. Introduction**

Inflammatory bowel diseases (IBD) are chronic diseases that share immune-mediated pathogenesis and relapsing course [1]. Crohn's disease (CD) and ulcerative colitis (UC) are the two main IBD types. The exact pathogenesis of IBD remains unknown. The most recent studies agree in identifying an individual genetic susceptibility strongly conditioned by environmental factors and by the interaction between intestinal microbiota and the body's immune response [2,3]. Changes in the epidemiology of IBD over time and in different geographical areas sugges<sup>t</sup> that environmental factors play an important role in inducing or modifying the expression of the disease [4]. Considering that IBD emerged in Western countries around the middle of the 20th century and the increased incidence of IBD in developing countries over the last 25 years, this epidemiological evolution is supposed to be linked to both the Westernization of the lifestyle and industrialization. Urbanization is associated with dietary changes, antibiotic use, hygienic status, microbial exposure and pollution, all implicated as

potential environmental risk factors for IBD [5]. A consequence of Westernization of the lifestyle seems to be dysbiosis, defined as a loss of diversity of composition of microbiome in an individual. Microbial diversity decreases in patients with CD compared to subjects without CD [6].

Biological drugs, first of all anti-tumor necrosis factor (TNF), are able to modify the natural history of numerous inflammatory diseases [7], in part by acting directly on inflammation and partly indirectly with mechanisms not ye<sup>t</sup> fully understood. Few studies have analysed the e ffect of adalimumab therapy on specific bacteria of intestinal microbiota in adult IBD patients [8].

The aim of our study was to analyse microbiome modifications and the association of microbiome characteristics with inflammatory parameters during the first six months of adalimumab therapy in adult patients with CD.

#### **2. Materials and Methods**

We performed a prospective study at the Gastroenterology Unit of "City of Health and Science of Turin", Italy. From May 2018 to March 2019 we recruited patients: (1) a ffected by CD with indications to treatment with adalimumab; (2) naive to anti-TNF drugs or other biological drugs; (3) older than or equal to 18 years; (4) on a typical Mediterranean diet; (5) who agreed to sign the informed consent to participate in the study. Exclusion criteria were: (1) recent (in the last month) use of probiotic therapy; (2) recent (in the last month) use of antibiotic therapy.
